Issues involving biomarkers in the study of the genetics of human cancer

The investigation of hereditary factors in human cancer was suggested from kindreds that exhibited aggregations of cancer consistent with Mendelian inheritance. A subset of cancer that exhibits strong familial tendencies is due to single genes that 'cause' cancer; more commonly, hereditary factors may influence tumorigenesis in a stepwise probabilistic rather than deterministic manner through a variety of mechanisms, e.g. influencing the disposition of carcinogens. The roles of both common susceptibility genes and rare 'familial' cancer genes are receiving increasing attention in the general population. Population-based studies designed to examine more common genetic variants differ from linkage-based studies. Candidate susceptibility genes may be studied by phenotype or genotype approaches, and the relative advantages and disadvantages of each approach are considered. The issue of gene-environment interaction, implicit in the concept of susceptibility genes, is considered. The influence of genetic factors on individual and attributable risk is addressed.